US8247511B2 - Water plasticized high refractive index polymer for ophthalmic applications - Google Patents
Water plasticized high refractive index polymer for ophthalmic applications Download PDFInfo
- Publication number
- US8247511B2 US8247511B2 US11/494,911 US49491106A US8247511B2 US 8247511 B2 US8247511 B2 US 8247511B2 US 49491106 A US49491106 A US 49491106A US 8247511 B2 US8247511 B2 US 8247511B2
- Authority
- US
- United States
- Prior art keywords
- methacrylate
- monomer
- copolymer
- intraocular lens
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime, expires
Links
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 229920002100 high-refractive-index polymer Polymers 0.000 title description 2
- 229920001577 copolymer Polymers 0.000 claims abstract description 70
- 239000000178 monomer Substances 0.000 claims abstract description 70
- -1 aryl acrylate Chemical compound 0.000 claims abstract description 37
- 238000000034 method Methods 0.000 claims abstract description 24
- 239000003431 cross linking reagent Substances 0.000 claims abstract description 21
- 239000000017 hydrogel Substances 0.000 claims abstract description 17
- 229920001519 homopolymer Polymers 0.000 claims abstract description 5
- 125000001424 substituent group Chemical group 0.000 claims abstract description 4
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Natural products C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 43
- STVZJERGLQHEKB-UHFFFAOYSA-N ethylene glycol dimethacrylate Substances CC(=C)C(=O)OCCOC(=O)C(C)=C STVZJERGLQHEKB-UHFFFAOYSA-N 0.000 claims description 35
- DBCAQXHNJOFNGC-UHFFFAOYSA-N 4-bromo-1,1,1-trifluorobutane Chemical compound FC(F)(F)CCCBr DBCAQXHNJOFNGC-UHFFFAOYSA-N 0.000 claims description 32
- RZVINYQDSSQUKO-UHFFFAOYSA-N 2-phenoxyethyl prop-2-enoate Chemical compound C=CC(=O)OCCOC1=CC=CC=C1 RZVINYQDSSQUKO-UHFFFAOYSA-N 0.000 claims description 31
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 claims description 27
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 claims description 27
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 13
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 238000005520 cutting process Methods 0.000 claims description 8
- 238000003754 machining Methods 0.000 claims description 7
- 229920001223 polyethylene glycol Polymers 0.000 claims description 7
- XFCMNSHQOZQILR-UHFFFAOYSA-N 2-[2-(2-methylprop-2-enoyloxy)ethoxy]ethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCOCCOC(=O)C(C)=C XFCMNSHQOZQILR-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- OLQFXOWPTQTLDP-UHFFFAOYSA-N 2-(2-hydroxyethoxy)ethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCOCCO OLQFXOWPTQTLDP-UHFFFAOYSA-N 0.000 claims description 5
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 5
- 125000004386 diacrylate group Chemical group 0.000 claims description 5
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- LCDOENXNMQXGFS-UHFFFAOYSA-N phenoxybenzene;prop-2-enoic acid Chemical compound OC(=O)C=C.C=1C=CC=CC=1OC1=CC=CC=C1 LCDOENXNMQXGFS-UHFFFAOYSA-N 0.000 claims description 4
- 238000005498 polishing Methods 0.000 claims description 4
- HMYDRWZDTWVLGO-UHFFFAOYSA-N (2,2-diethoxy-2-hydroxyethyl) 2-methylprop-2-enoate Chemical compound CCOC(O)(OCC)COC(=O)C(C)=C HMYDRWZDTWVLGO-UHFFFAOYSA-N 0.000 claims description 3
- URYWXMHZLSZSNE-UHFFFAOYSA-N (2,2-diethoxy-2-methoxyethyl) 2-methylprop-2-enoate Chemical compound CCOC(OCC)(OC)COC(=O)C(C)=C URYWXMHZLSZSNE-UHFFFAOYSA-N 0.000 claims description 3
- VDYWHVQKENANGY-UHFFFAOYSA-N 1,3-Butyleneglycol dimethacrylate Chemical compound CC(=C)C(=O)OC(C)CCOC(=O)C(C)=C VDYWHVQKENANGY-UHFFFAOYSA-N 0.000 claims description 3
- DAVVKEZTUOGEAK-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethyl 2-methylprop-2-enoate Chemical compound COCCOCCOC(=O)C(C)=C DAVVKEZTUOGEAK-UHFFFAOYSA-N 0.000 claims description 3
- YXYJVFYWCLAXHO-UHFFFAOYSA-N 2-methoxyethyl 2-methylprop-2-enoate Chemical compound COCCOC(=O)C(C)=C YXYJVFYWCLAXHO-UHFFFAOYSA-N 0.000 claims description 3
- XOJWAAUYNWGQAU-UHFFFAOYSA-N 4-(2-methylprop-2-enoyloxy)butyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCCCOC(=O)C(C)=C XOJWAAUYNWGQAU-UHFFFAOYSA-N 0.000 claims description 3
- SAPGBCWOQLHKKZ-UHFFFAOYSA-N 6-(2-methylprop-2-enoyloxy)hexyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCCCCCOC(=O)C(C)=C SAPGBCWOQLHKKZ-UHFFFAOYSA-N 0.000 claims description 3
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000003011 styrenyl group Chemical class [H]\C(*)=C(/[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- KAKZBPTYRLMSJV-UHFFFAOYSA-N vinyl-ethylene Natural products C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 230000000887 hydrating effect Effects 0.000 claims description 2
- 229920001567 vinyl ester resin Polymers 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 abstract description 18
- 229920000642 polymer Polymers 0.000 description 29
- 239000000463 material Substances 0.000 description 25
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 230000036571 hydration Effects 0.000 description 13
- 238000006703 hydration reaction Methods 0.000 description 13
- 239000007864 aqueous solution Substances 0.000 description 11
- 230000009477 glass transition Effects 0.000 description 11
- 239000000203 mixture Substances 0.000 description 9
- 238000006116 polymerization reaction Methods 0.000 description 9
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2,2'-azo-bis-isobutyronitrile Substances N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 239000003999 initiator Substances 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 230000003287 optical effect Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 239000004971 Cross linker Substances 0.000 description 4
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 239000002981 blocking agent Substances 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- SUPCQIBBMFXVTL-UHFFFAOYSA-N ethyl 2-methylprop-2-enoate Chemical compound CCOC(=O)C(C)=C SUPCQIBBMFXVTL-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 4
- 239000004926 polymethyl methacrylate Substances 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- SBYMUDUGTIKLCR-UHFFFAOYSA-N 2-chloroethenylbenzene Chemical group ClC=CC1=CC=CC=C1 SBYMUDUGTIKLCR-UHFFFAOYSA-N 0.000 description 3
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000002837 carbocyclic group Chemical group 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000000465 moulding Methods 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- SSGLEMWHDJHHNH-UHFFFAOYSA-N (2-ethylphenyl) 2-methylprop-2-enoate Chemical compound CCC1=CC=CC=C1OC(=O)C(C)=C SSGLEMWHDJHHNH-UHFFFAOYSA-N 0.000 description 2
- OUOHOJDXEPUCDT-UHFFFAOYSA-N (2-ethylphenyl) prop-2-enoate Chemical compound CCC1=CC=CC=C1OC(=O)C=C OUOHOJDXEPUCDT-UHFFFAOYSA-N 0.000 description 2
- OHPOBBXVVREUAF-UHFFFAOYSA-N (2-hexylphenyl) 2-methylprop-2-enoate Chemical compound CCCCCCC1=CC=CC=C1OC(=O)C(C)=C OHPOBBXVVREUAF-UHFFFAOYSA-N 0.000 description 2
- MADYBBZSBQFZRP-UHFFFAOYSA-N (2-hexylphenyl) prop-2-enoate Chemical compound CCCCCCC1=CC=CC=C1OC(=O)C=C MADYBBZSBQFZRP-UHFFFAOYSA-N 0.000 description 2
- AOUAMFARIYTDLK-UHFFFAOYSA-N (4-methylphenyl) 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OC1=CC=C(C)C=C1 AOUAMFARIYTDLK-UHFFFAOYSA-N 0.000 description 2
- ZALFZMYXGFDRIW-UHFFFAOYSA-N (4-methylphenyl)methyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCC1=CC=C(C)C=C1 ZALFZMYXGFDRIW-UHFFFAOYSA-N 0.000 description 2
- ITKPEKLPFWJSOJ-UHFFFAOYSA-N 2-(2-chlorophenyl)ethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCC1=CC=CC=C1Cl ITKPEKLPFWJSOJ-UHFFFAOYSA-N 0.000 description 2
- YEQRGDXTQPUPMJ-UHFFFAOYSA-N 2-(2-methylphenyl)ethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCC1=CC=CC=C1C YEQRGDXTQPUPMJ-UHFFFAOYSA-N 0.000 description 2
- CAWQOFMAJKVFII-UHFFFAOYSA-N 2-(3-chlorophenyl)ethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCC1=CC=CC(Cl)=C1 CAWQOFMAJKVFII-UHFFFAOYSA-N 0.000 description 2
- JPTHRABUTMVMHR-UHFFFAOYSA-N 2-(3-methylphenyl)ethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCC1=CC=CC(C)=C1 JPTHRABUTMVMHR-UHFFFAOYSA-N 0.000 description 2
- ACZLUEDVQBUFQM-UHFFFAOYSA-N 2-(3-phenylphenyl)ethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCC1=CC=CC(C=2C=CC=CC=2)=C1 ACZLUEDVQBUFQM-UHFFFAOYSA-N 0.000 description 2
- XUXKNMQGQVAAJA-UHFFFAOYSA-N 2-(4-benzylphenyl)ethyl 2-methylprop-2-enoate Chemical compound C1=CC(CCOC(=O)C(=C)C)=CC=C1CC1=CC=CC=C1 XUXKNMQGQVAAJA-UHFFFAOYSA-N 0.000 description 2
- XHMBRNYBXTUYJN-UHFFFAOYSA-N 2-(4-bromophenyl)ethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCC1=CC=C(Br)C=C1 XHMBRNYBXTUYJN-UHFFFAOYSA-N 0.000 description 2
- DANPNQMLVGTTRA-UHFFFAOYSA-N 2-(4-chlorophenyl)ethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCC1=CC=C(Cl)C=C1 DANPNQMLVGTTRA-UHFFFAOYSA-N 0.000 description 2
- IOFBPLNRQQDCSU-UHFFFAOYSA-N 2-(4-methoxyphenyl)ethyl 2-methylprop-2-enoate Chemical compound COC1=CC=C(CCOC(=O)C(C)=C)C=C1 IOFBPLNRQQDCSU-UHFFFAOYSA-N 0.000 description 2
- HKGJTSSOXHQYDQ-UHFFFAOYSA-N 2-(4-methylphenyl)ethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCC1=CC=C(C)C=C1 HKGJTSSOXHQYDQ-UHFFFAOYSA-N 0.000 description 2
- XKTDLXROKPMKQF-UHFFFAOYSA-N 2-(4-phenylphenyl)ethyl 2-methylprop-2-enoate Chemical compound C1=CC(CCOC(=O)C(=C)C)=CC=C1C1=CC=CC=C1 XKTDLXROKPMKQF-UHFFFAOYSA-N 0.000 description 2
- WIGVBGZTCYJIIS-UHFFFAOYSA-N 2-(4-propylphenyl)ethyl 2-methylprop-2-enoate Chemical compound CCCC1=CC=C(CCOC(=O)C(C)=C)C=C1 WIGVBGZTCYJIIS-UHFFFAOYSA-N 0.000 description 2
- ILZXXGLGJZQLTR-UHFFFAOYSA-N 2-phenylethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCCC1=CC=CC=C1 ILZXXGLGJZQLTR-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 208000002177 Cataract Diseases 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
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- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
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- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
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- 125000001931 aliphatic group Chemical group 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
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- 230000008901 benefit Effects 0.000 description 2
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- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
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- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
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- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 235000010338 boric acid Nutrition 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 1
- 229910003460 diamond Inorganic materials 0.000 description 1
- 239000010432 diamond Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000004442 gravimetric analysis Methods 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- LNMQRPPRQDGUDR-UHFFFAOYSA-N hexyl prop-2-enoate Chemical compound CCCCCCOC(=O)C=C LNMQRPPRQDGUDR-UHFFFAOYSA-N 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 150000002734 metacrylic acid derivatives Chemical class 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000002985 plastic film Substances 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 229920005604 random copolymer Polymers 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 229910052717 sulfur Chemical group 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B1/00—Optical elements characterised by the material of which they are made; Optical coatings for optical elements
- G02B1/04—Optical elements characterised by the material of which they are made; Optical coatings for optical elements made of organic materials, e.g. plastics
-
- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B1/00—Optical elements characterised by the material of which they are made; Optical coatings for optical elements
- G02B1/04—Optical elements characterised by the material of which they are made; Optical coatings for optical elements made of organic materials, e.g. plastics
- G02B1/041—Lenses
- G02B1/043—Contact lenses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/14—Eye parts, e.g. lenses, corneal implants; Implanting instruments specially adapted therefor; Artificial eyes
- A61F2/16—Intraocular lenses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/16—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F212/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring
- C08F212/02—Monomers containing only one unsaturated aliphatic radical
- C08F212/04—Monomers containing only one unsaturated aliphatic radical containing one ring
- C08F212/06—Hydrocarbons
- C08F212/08—Styrene
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
- C08F220/26—Esters containing oxygen in addition to the carboxy oxygen
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
- C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
- C08F220/10—Esters
- C08F220/26—Esters containing oxygen in addition to the carboxy oxygen
- C08F220/30—Esters containing oxygen in addition to the carboxy oxygen containing aromatic rings in the alcohol moiety
- C08F220/301—Esters containing oxygen in addition to the carboxy oxygen containing aromatic rings in the alcohol moiety and one oxygen in the alcohol moiety
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F222/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides, or nitriles thereof
-
- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B1/00—Optical elements characterised by the material of which they are made; Optical coatings for optical elements
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/16—Materials or treatment for tissue regeneration for reconstruction of eye parts, e.g. intraocular lens, cornea
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F212/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring
- C08F212/02—Monomers containing only one unsaturated aliphatic radical
- C08F212/04—Monomers containing only one unsaturated aliphatic radical containing one ring
- C08F212/14—Monomers containing only one unsaturated aliphatic radical containing one ring substituted by heteroatoms or groups containing heteroatoms
- C08F212/16—Halogens
- C08F212/18—Chlorine
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F222/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides, or nitriles thereof
- C08F222/10—Esters
- C08F222/1006—Esters of polyhydric alcohols or polyhydric phenols
- C08F222/102—Esters of polyhydric alcohols or polyhydric phenols of dialcohols, e.g. ethylene glycol di(meth)acrylate or 1,4-butanediol dimethacrylate
Definitions
- This application relates to the field of organic chemistry, polymer chemistry, materials science and ophthalmic devices.
- this invention relates to acrylic copolymers and foldable intraocular lenses (foldable IOLs) made thereof.
- Hydrogel materials are rigid when dry but can be hydrated with large amounts of water (generally 20-70% by weight) become soft and pliable. However, the hydration process tends to the refractive index of the hydrated polymer. For example, currently recognized hydrogels have a refractive index that is generally less than about 1.48. In addition to adversely affecting refractive index, the absorbed water also significantly increases the diameter and thickness of the IOLs, for example, by as much as about 15 percent.
- the current invention provides such a polymer and a method of manufacturing a foldable IOL from it.
- an aspect of the present invention is a method of manufacturing an intraocular lens comprising:
- the foldable intraocular lens has an equilibrium water content from about 2 wt % to about 8 wt %.
- the foldable intraocular lens has an equilibrium water content of about 4 wt %.
- the method further comprises a UV blocker.
- the method further comprises a blue light blocker.
- the intraocular lens is a 20 diopter lens and has a central thickness less than about 0.4 mm.
- the rigid intraocular lens is hydrated by: placing the lens in an aqueous solution;
- the rigid intraocular lens is hydrated by placing it in an aqueous solution, gradually increasing the temperature of the aqueous solution to 50° C., holding the temperature at 50° C. for about 24 hours and then gradually decreasing the temperature to about room temperature.
- machining the rigid intraocular lens comprises lathe cutting the lens from a rigid sheet or rod of the copolymer and polishing the cut lens.
- the first monomer is selected from the group consisting of ethylene glycol phenyl ether acrylate (EGPEA), poly(ethylene glycol) phenyl ether acrylate ((polyEG)PEA), phenyl methacrylate, 2-ethylphenyl methacrylate, 2-ethylphenyl acrylate, hexylphenyl methacrylate, hexylphenyl acrylate, benzyl methacrylate, 2-phenylethyl methacrylate, 4-methylphenyl methacrylate, 4-methylbenzyl methacrylate, 2-(2-methylphenyl )ethyl methacrylate, 2-(3-methylphenyl )ethyl methacrylate, 2-(4-methylphenyl)ethyl methacrylate, 2-(4-propylphenyl)ethyl methacrylate.
- EPEA ethylene glycol phenyl ether acrylate
- polyEG poly(ethylene
- the first monomer is selected from the group consisting of EGPEA and (polyEG)PEA.
- the second monomer is selected from the group consisting of chlorostyrene and styrene.
- the second monomer is styrene.
- the third monomer is selected from the group consisiting of hydroxyethyl methacrylate (HEMA), hydroxyethoxyethyl methacrylate (HEEMA), hydroxydiethoxyethyl methacrylate, methoxyethyl methacrylate, methoxyethoxyethyl methacrylate, methoxydiethoxyethyl methacrylate, N-vinyl-2-pyrrolidone, methacrylic acid and vinyl alcohol.
- HEMA hydroxyethyl methacrylate
- HEEMA hydroxyethoxyethyl methacrylate
- HEEMA hydroxydiethoxyethyl methacrylate
- methoxyethyl methacrylate methoxyethoxyethyl methacrylate
- methoxydiethoxyethyl methacrylate methacrylic acid and vinyl alcohol.
- the third monomer is selected from the group consisting of hydroxyethyl methacrylate (HEMA), hydroxyethoxyethyl methacrylate (HEEMA).
- HEMA hydroxyethyl methacrylate
- HEEMA hydroxyethoxyethyl methacrylate
- the cross-linking agent is selected from the group consisting of a divinyl compound, a vinyl ester of an acrylate or methacrylate, an allyl ester of an acrylate or methacrylate, a diacrylate, a dimethacrylate or an acrylate/methacrylate.
- the cross-linking agent is selected from the group consisting of ethylene glycol dimethacrylate (EGDM), diethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, 1-3-propanedioldimethacrylate, 1,6-hexanediol dimethacrylate, 1,3-butanediol dimethacrylate and 1,4-butanediol dimethacrylate.
- EGDM ethylene glycol dimethacrylate
- diethylene glycol dimethacrylate polyethylene glycol dimethacrylate
- polyethylene glycol dimethacrylate 1-3-propanedioldimethacrylate
- 1,6-hexanediol dimethacrylate 1,3-butanediol dimethacrylate
- 1,4-butanediol dimethacrylate 1,4-butanediol dimethacrylate.
- the cross-linking agent is ethylene glycol dimethacrylate.
- Table 1 shows the composition of various copolymers of this invention and provides some physical characteristics of the copolymers.
- Table 2 shows some materials of which intraocular devises are currently manufactured and likewise provides some of their physical characteristics by way of comparison with the copolymers in Table 1.
- Table 3 shows the dimensional stability of the copolymer of this invention when taken from the dry state to the hydrated state.
- the current invention relates to foldable, high refractive index polymers that can be machined using lathe cutting and other conventional techniques such as those used in the manufacture of polymethyl methacrylate (PMMA) lenses to form IOLs.
- PMMA polymethyl methacrylate
- the polymers should be useful for the manufacture of ophthalmic devices such as contact lenses, keratoprostheses, intracorneal lenses (ICL) and corneal rings or inlays, etc. In particular they are useful for the manufacture of IOLs.
- An advantageous property of the polymers of this invention is that they are hard enough in their unhydrated state to machine at room temperature but can be hydrated to provide soft, foldable IOLs having high refractive indices. Further, they can be hydrated to a suitably flexible state using a relatively small amount of water. The use of minimal water ameliorates the adverse effects of hydration on the polymer's mechanical and optical properties such as those observed with other high water content hydrogel lens materials. Dimensional changes in the end product are also minimized.
- Another advantage of the polymers of the present invention is that lenses can be tumble polished to provide smooth and rounded edges. This is facilitated by the relatively high glass transition temperature (Tg) of the material as well as other mechanical properties.
- the polymers of the present invention are copolymers comprising at least three monomers.
- One of the monomers is an aryl acrylate or methacrylate (acrylates and methacrylates are referred to herein by the shorthand designation (meth)acrylate)
- one is a non-(meth)acrylate aryl group-containing monomer wherein the aryl group is substituted with an ethylenic unsaturation (and may be further substituted as well)
- the third is a monomer containing one ethylenic unsaturation and which, as a homopolymer, forms a high water content hydrogel.
- the copolymer may be cross-linked if desired.
- an “ethylenic unsaturation” simply refers to an aliphatic —C ⁇ C— moiety which may occur anywhere in the molecule but preferably at present is at a terminal position, i.e., is a —C ⁇ CH 2 group.
- weight percent (wt %) of monomers refers to the percentage calculated as the weight of the monomer in the polymerization reaction mixture divided by the total weight of monomers in the reaction.
- wt % of the constitutional unit based on the particular monomer will be slightly different than preceding but the difference is inconsequential.
- the phrase “in the copolymer” will be used when discussing monomer weight percentages but it is understood that the number is actually derived from the foregoing.
- a copolymer of this invention may be a random or block copolymer.
- each monomer in the copolymer is selected to provide a substantially rigid polymer having a glass transition temperature of at least about normal room temperature. It is presently preferred that each of the three monomers is present in the copolymer in an amount of at least about 10 wt %, more preferably, at least about 20 wt %. In a presently preferred embodiment, the copolymer comprises:
- a third monomer such as, without limitation, hydroxy ethyl methacrylate, hydroxyethoxy ethyl methacrylate, or methacrylic acid
- a crosslinking agent such as a diacrylate or a dimethacrylate.
- the copolymer resulting from the polymerization of the above monomers should, when hydrated, be foldable at or above normal room temperature, i.e., above about 15° C. and should have a refractive index greater than about 1.50.
- aryl refers to a carbocyclic (all carbon) ring or two or more fused (rings that share two adjacent carbon atoms) carbocyclic rings that have a fully delocalized pi-electron system.
- aryl also refers to a heteroaryl ring, that is, a ring or two or more fused rings at least one of which contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur wherein the ring or rings likewise have a fully delocalized pi-electron system.
- Examples of carbocyclic aryl groups include, without limitation, benzene, naphthalene and azulene.
- heterocyclic aryl rings include, but are not limited to, furan, thiophene, pyrrole, thiazole, imidazole, oxazole, isoxazole, isothiazole, triazole, thiadiazole, pyridine, pyrimidine, pyrazine, and triazine,
- aryl (meth)acrylates monomers of this invention have the formula
- Q may be, without limitation, ethylene glycol phenyl ether, poly(ethylene glycol phenyl ether), phenyl, 2-ethylphenyl, hexylphenyl, benzyl, 2-phenylethyl, 4-methylphenyl, 4-methylbenzyl, 2-(2-methyphenyl)ethyl, 2-(3-methylphenyl)ethyl, 2(4-methylphenyl)ethyl, 2-(4-propylphenyl)ethyl, 2-(4-(1-methylethyl)phenyl)ethyl, 2-(4-methoxyphenyl)ethyl, 2-(4-cyclohexylphenyl)ethyl, 2-(2-chlorophenyl)ethyl, 2-(3-chlorophenyl)ethyl 2-(4-chlorophenyl)ethyl, 2-(4-bromophenyl)eth, 2-
- suitable (meth)acrylate monomers include, without limitation: ethylene glycol phenyl ether acrylate (EGPEA), poly(ethylene glycol) phenyl ether acrylate ((polyEG)PEA), phenyl methacrylate, 2-ethylphenyl methacrylate, 2-ethylphenyl acrylate, hexylphenyl methacrylate, hexylphenyl acrylate, benzyl methacrylate, 2-phenylethyl methacrylate, 4-methylphenyl methacrylate, 4-methylbenzyl methacrylate, 2-(2-methylphenyl)ethyl methacrylate, 2-(3-methylphenyl)ethyl methacrylate, 2-(4-methylphenyl)ethyl methacrylate, 2-(4-propylphenyl)ethyl methacrylate.
- EPEA ethylene glycol phenyl ether acrylate
- polyEG poly(ethylene
- aryl (meth)acrylates that can be used to prepare the copolymers herein; all such aryl (meth)acrylates are within the scope of this invention.
- EGPEA and (polyEG)PEA are presently preferred aryl (meth)acrylates.
- the first monomer is present in the polymer in an amount sufficient to provide high refractive index, moderate water uptake, and enhanced backbone rigidity.
- the first monomer comprises at least about 10 wt % of the composition; more preferably, at least about 20 wt % and, presently most preferably, at least about 30 wt %.
- the amount of the first monomer should also be sufficient to avoid an undesirably low glass transition temperature in the resulting copolymer.
- the first monomer comprises less than about 60 wt % of the copolymer; more preferably, less than about 50 wt % and presently most preferably, less than about 45 wt %.
- the second monomer comprises an aryl group that is substituted by at least a group having an ethylenic unstaturation but the monomer is not an aryl meth(acrylate).
- a suitable second monomer is optionally substituted styrene. If substituted, the substituent is selected from the group consisting of halogen (Br, Cl and/or F), lower alkyl (e.g. methyl, ethyl, propyl, butyl, isopropyl) and/or lower alkoxy groups.
- halogen Br, Cl and/or F
- lower alkyl e.g. methyl, ethyl, propyl, butyl, isopropyl
- lower alkoxy groups e.g. methyl, ethyl, propyl, butyl, isopropyl
- alkyl refers to a straight or branched chain fully saturated (no double or triple bonds) hydrocarbon (carbon and hydrogen only) group.
- alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertiary butyl, pentyl, hexyl, ethenyl, propenyl, butenyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
- alkyl includes “alkylene” groups, which refer to straight or branched fully saturated hydrocarbon groups having two rather than one open valences for bonding to other groups.
- alkylene groups include, but are not limited to methylene, —CH 2 —, ethylene, —CH 2 CH 2 —, propylene, —CH 2 CH 2 CH 2 —, n-butylene, —CH 2 CH 2 CH 2 CH 2 —, sec-butylene, —CH 2 CH 2 CH(CH 3 )— and the like.
- aliphatic is considered synonymous with “alkyl.”
- alkoxy refers to an —O-alkyl group.
- a presently preferred second monomer is chlorostyrene and presently most preferred is styrene itself.
- the second monomer is present in the copolymer in an amount sufficient to increase the glass transition temperature of the resulting copolymer to a desired working temperature. Without being held to any particular theory, it is believed that the second monomer also provides a higher refractive index and hydrophobicity due to its aromatic ring.
- the second monomer comprises at least about 10 wt % of the copolymer; more preferably at least about 15 wt % and most preferably at present, at least about 20 wt %.
- the second monomer should be present in an amount that achieves the foregoing objectives but does not adversely affect the refractive index, optical clarity, or other desirable properties of the copolymer.
- the second monomer comprises less than about 60 wt % of the copolymer; more preferably less than about 40 wt % and; most preferably at present, less than about 30 wt %.
- the third monomer comprises a compound that contains one ethylenic unsaturation so that it can be included in the polymer backbone and, further, as a homopolymer, can form a high water content hydrogel.
- the third monomer comprises a methacrylate without an aromatic substituent.
- Suitable third monomers include, without limitation, hydroxyethyl methacrylate (HEMA), hyd roxyethoxyethyl methacrylate (HEEMA), hydroxydiethoxyethyl methacrylate, methoxyethyl methacrylate, methoxyethoxyethyl methacrylate, methoxydiethoxyethyl methacrylate, N-vinyl-2-pyrrolidone, methacrylic acid and vinyl alcohol (which may be incorporated into the copolymer as vinyl acetate and then hydrolyzed).
- HEMA and HEEMA are preferred third monomers.
- the third monomer is present in an amount sufficient to render the resulting copolymer hydratable at the level of about 10% or less.
- the third monomer is present in at least about 10 wt % of the composition; more preferably at least about 20 wt % and, most preferably at present, at least about 25 wt %.
- the third monomer should be present in an amount low enough to avoid significant expansion of the copolymer on hydration.
- the third monomer comprises less than about 60 wt %, more preferably less than about 50 wt % and, most preferably at present, less than about 40 wt % of the copolymer.
- the copolymer may also include a crosslinking agent.
- Crosslinking agents for the purpose of this invention comprise compounds with two or more sites of ethylenic unsaturation. Preferably at present, both ethylenic unsaturation sites are at terminal positions on the crosslinking agent.
- the crosslinking agent may be, for example without limitation, a divinyl compound, a vinyl or allyl ester of a (methacrylate), a diacrylate, a dimethacrylate or a combiation of acrylate and methacrylate.
- the crosslinking agent comprises a diacrylate, a dimethacrylate or an acrylate/methacrylate, that is an agent wherein one of the ethylenic unsaturations is contained in an acryate and another in a methacrylate.
- Particularly preferred crosslinking agents at present have the following formula:
- crosslinking agents of this invention include, without limitation, ethylene glycol dimethacrylate (EGDM), diethylene glycol dimethacrylate, polyethylene glycol dimethacrylate, 1-3-propanedioldimethacrylate, 1,6-hexanediol dimethacrylate, 1,3-butanediol dimethacrylate and 1,4-butanediol dimethacrylate. Most preferred at presnt is ethylene glycol dimethacrylate.
- the crosslinking agent should be present in an amount sufficient to permit the hydrated copolymer to return to its original shape after being folded.
- the crosslinking agent comprises at least about 1.0 wt % of the composition; more preferably, at least about 3.0 wt %.
- the crosslinking agent should be present in an amount low enough to avoid making the copolymer too rigid or brittle.
- the crosslinking agent comprises less than about 10 wt % of the copolymer, more preferably at present less than about 5 wt %.
- UV blocking agents such as ultraviolet (UV) blocking agents, blue light blocking agents, etc.
- additives such as ultraviolet (UV) blocking agents, blue light blocking agents, etc.
- UV ultraviolet
- blue light blocking agents optionally may be added to the copolymer-containing composition depending upon the intended application.
- Such may be added during the polymerization reaction any may in fact contain an ethylenic unsaturation such that it becomes incorporated into the backbone of the copolymer or it may be added after polymerization and before being formed into a machinable configuration.
- Representative UV absorbing materials include those disclosed, for example, in column 5, lines 3-29 of U.S. Pat. No. 5,433,746 to Namong et al., which is incorporated by reference as if fully set forth herein.
- Suitable UV absorbers include, for example without limitation, benzophenone, vinyl benzophenone, and benzotriazole.
- the UV absorbing material is preferably added in a concentration less than about 1 percent based on the total weight of the copolymer.
- the copolymers of the invention may be produced using conventional polymerization techniques.
- the monomers can be blended together and heated to an elevated temperature to facilitate the polymerization reaction.
- Catalysts and/or initiators selected well-known to those skilled in the polymerization art may be included in the monomer mix in order to promote, and/or increase the rate of, the polymerization reaction.
- catalysts/initiators include, without limitation, free radical initiators such as 2-2′-azobisisobutyronitrile (AIBN), benzoyl peroxide, acetyl peroxide, lauryl peroxide and t-butyl peroxide. At present, 2-2′-azobisisobutyronitrile (AIBN) is a preferred initiator.
- a method of manufacturing ophthalmic devices using a copolymer of this invention may comprise the following: a copolymer, which has a glass transition temperature greater than about normal room temperature, i.e., about 15° C. or 60° F., and a refractive index greater than about 1.50; that is, a copolymer of this invention, is provided.
- the copolymer in its unhydrated, i.e., rigid, state is formed into a rigid ophthalmic device having the desired dimensions.
- the ophthalmic device is then hydrated to form a foldable ophthalmic device.
- the hydrated copolymer has an equilibrium water concentration less than about 10 wt % and a refractive index greater than about 1.50.
- a copolymer of the present invention may be formed into the shape of sheet or rod for the purpose of manufacturing an ophthalmic device of this invention.
- the ophthalmic device is cut to a desired dimension and diopter from a sheet or the rod of copolymer using standard lathe cutting techniques at room temperature and the is polished, likewise using standard techniques such as tumble polishing.
- the ophthalmic device for example and preferably at present an IOL, is then hydrated. This may be achieved by soaking it in an aqueous solution (water or saline), preferably at an elevated temperature (e.g. between 20-100° C.), for a sufficient time to allow the polymer to reach its equilibrium water content.
- an aqueous solution water or saline
- an elevated temperature e.g. between 20-100° C.
- the equilibrium water content is the amount of water that the copolymer can contain at about body temperature, that is, about 37° C.
- the copolymer after being machined into an ophthalmic device may be placed in an aqueous solution, the temperature may be increased to about 40° C. and then held at about 40° C. for about 10 minutes. Next, the temperature may be gradually increased to about 60° C., held there for about one hour and then gradually decreased to about room temperature. It is understood that this is simply one way of achieving equilibrium water content for a polymer of this invention. Those skilled in the art will, based on the disclosure here, readily recognize other protocols for achieving equilibrium water concentration of these copolymers; all such protocols are within the scope of this invention.
- isotonic saline refers to a salt, normally sodium chloride, dissolved in water, the amount of salt being substantially the same as that in bodily fluids. For use in the eye, this is approximately 0.8-0.9% w/v (weight per unit volume) of sodium chloride in water. In the metric system, w/v is the same as w/w since a unit volume of water, that is one cubic centimeter, weight one gram.
- the isotonic saline may be buffered to match intraocular pH by the addition of boric acid and sodium borate or sodium phosphate and potassium phosphate (phosphate-buffered saline, PBS).
- isotonic saline solutions for use in the intraocular lens and method of this invention are phosphate-buffered saline, such as, without limitation, Dulbecco's buffered phosphate solution; balanced salt solutions such as, again without limitation, Hank's balanced salt solution and Earle's balanced salt solution; and blood bank saline, an approximately 0.85 to 0.9% sodium chloride solution buffered to blood pH (7.0-7.2).
- phosphate-buffered saline such as, without limitation, Dulbecco's buffered phosphate solution
- balanced salt solutions such as, again without limitation, Hank's balanced salt solution and Earle's balanced salt solution
- blood bank saline an approximately 0.85 to 0.9% sodium chloride solution buffered to blood pH (7.0-7.2).
- An IOL or other ophthalmic device fabricated from a polymer of the present invention should not significantly change shape or dimensions when hydrated. That is, there should be no statistically significant difference between the diameter and thickness of the dry device and that of the hydrated device.
- copolymers of the invention have a unique combination of desirable characteristics: high refractive index, good mechanical properties, high glass transition temperature, optical clarity, hydratability, and foldability once hydrated. Particularly advantageous is the fact that the copolymers of this invention are foldable at or above normal room temperature (i.e., at or above about 15° C.) despite having a glass transition temperature above room temperature and also that, in the hydrated state, they have a refractive index (RI) of about 1.50 or higher.
- RI refractive index
- the refractive power of a lens is a function of its shape and the inherent refractive index of the material of which it is made. In general, the higher the refractive index, the better the material, all other factors being equal.
- a lens made from a material having a higher refractive index can be thin and provide the same refractive power as a thicker lens made from a material having a relatively lower refractive index. Thinner lenses are easier to insert and cause less traumatic injury during surgery. Refractive indices of at least 1.50 have been attained with copolymers of the present invention.
- a dry copolymer of this invention due in part to its glass transition temperature, is rigid but not brittle. This permits cutting and polishing (i.e., machining) of objects, e.g., lenses, at room temperature rather than having to mold them or shape them at cryogenic temperatures as in the prior art. In fact, at room temperature the hydrated polymers of this invention can be bent 180 degrees without cracking.
- an ophthalmic device made from a polymer of this invention facilitates forming a lens having the minimal central thickness allowed by the refractive index of the polymer.
- a thinner lens can be produced from a copolymer of the invention than from material having the same refractive index but which must be molded into a desired shape.
- a 20 diopter lens may be produced from a polymer of this invention having a central thickness less than about 0.8 mm.
- the thinness of the lens permits it to be inserted through an incision as small as about 2 mm, even less. This is a significant improvement over the current state of the art in the field of ophthalmic surgery where much larger incisions are generally required for lens insertion.
- the glass transition temperature (Tg) of a copolymer of this invention is preferably greater than about 15° C. so that it is workable by conventional cutting and lathing techniques. That is, at room temperature, the copolymer is rigid enough to be machined. Preferably, the Tg is greater than about 15° C., more preferably greater than about 25° C., and most preferably at present, greater than about 30° C.
- the Tg of a copolymer of this invention may be determined using any means accepted in the art but it is noted that different techniques can lead to sometimes substantially different results. For the purposes of this invention dynamic mechanical analysis is presently preferred.
- a hydrated copolymer of this invention will have an equilibrium water content (EWC) less than about 10 wt %, preferably less than about 8% wt %, even more preferably less than about 5 wt % and, most preferably at present, 4 wt % or less. More particularly, at present a hydrated copolymer of this invention has an equilibrium water concentration of from about 3 wt % to about 10 wt %, preferably from about 4 wt % to about 8 wt % and, presently most preferably, about 4 wt %. Such a low water uptake allows effective hydration without adverse affect on the mechanical or optical properties of the foldable lens.
- EWC equilibrium water content
- the copolymers of the invention tend to expand less than about 10 volume percent during hydration; preferably the volume percent expansion upon hydration is less than about 5%. Expansion percent is calculated by measuring the difference in dimension of standard buttons made of the copolymer before and after hydration.
- An artificial lens manufactured from a copolymer of this invention may be inserted into an eye using the same 2 mm incision currently used for cataract surgery. No sutures may be required.
- a method of implanting an IOL in an eye may comprise providing a hydrated IOL comprising a copolymer of this invention and injecting it into the eye by means of a syringe, preferable through an incision less than about 2 mm in length.
- the lens may be inserted using a device, for example, like that described in U.S. Pat. No. 4,715,373, which is incorporated as if fully set forth herein.
- the shape of the fixation system used to position the IOL in the eye is not critical to this invention.
- the copolymers may be used in a foldable lens having a variety of fixation systems. See, for example, U.S. Pat. No. 5,776,191, which is likewise incorporated as if fully set forth herein for a discussion of fixation systems for IOLs.
- Various copolymers were prepared by mixing the following ingredients under reduced pressure: a first, second and third monomeric component, a crosslinker and a polymerizable UV blocking agent.
- a first, second and third monomeric component for example without limitation, vinyl benzotriazole at a total concentration of 0.3% by weight may be used as a UV blocking agent.
- a free radical initiator 2-2′-azobisisobutyronitrile (AIBN)
- AIBN 2-2′-azobisisobutyronitrile
- the monomer solution was mixed in a glass flask using a magnetic stir bar for 30 minutes.
- the solution was filtered through a 0.2 micron ( ⁇ ) filter and injected into a sheet mold comprising two glass plates held together with spring clips and separated by a plastic gasket.
- the mold was then placed in a water bath for 10 hours at 60° C., removed and post-cured at 95° C. for 12 hours. A clear, hard polymer sheet was obtained.
- Intraocular lenses of various diopters (5, 10, 20, and 34) were cut from the rigid plastic sheet using conventional machining techniques such as those employed in the manufacture of polymethylmethacrylate (PMMA) IOLs.
- PMMA polymethylmethacrylate
- the IOLs were tumble polished for 2 days at 20° C.
- the polished lenses were rinsed with ultra-pure water. At this stage the IOLs are still hard and non-foldable.
- the IOLs were then placed in individual vials filled with saline solution.
- the vials were placed in a temperature controlled oven and subjected to the following conditioning cycle: increase temperature from 20° C. to 40° C. at a rate of 10° C. per hour. Hold at 40° C. for 30 minutes. Increase temperature to 60° C. at a rate of 10° C. per hour. Hold at 60° C. for 4 hours. Decrease temperature to room temperature (approximately 20° C.) at 10° C. per hour. At this point the IOLs were soft and easily foldable and had excellent optical properties. Lens dimensions (optic size, thickness, diameter) did not change significantly with hydration. The surface and edges of the samples were found to be very smooth.
- Table 2 shows some lenses made of materials other than the copolymers of this invention for comparison purposes.
- machinability refers to cutting the unhydrated material with a lathe in which a diamond tool comes in contact with the material while rotating at high speed.
- Good machinability means the material cuts cleanly into disks so the radii and dimensions of the final product may be selected in advance.
- Fair machinability means the material can be machined if environmental parameters can be controlled, for example, by decreasing the temperature.
- Poor machinability means the material tends to deform or break during lathe cutting, but it is still machinable if environmental parameters are controlled.
- Not machinable means the material cannot be cut with a lathe and must be formed using methods such as molding.
- “Foldability” refers to the ability to bend the material as much as about 180° without breaking once the material has been hydrated.
- Good foldability means the material can be easily folded using forceps when the material is cut into a disk about the size of a standard lens.
- Fair foldability means a hydrated disk of the material folds when applying little force.
- Poor foldability means the hydrated disk folds without breaking when a greater force is applied.
- Example 2 A hydration study was conducted to assess the change in dimension after complete hydration. Twenty samples of each formulation described in Example 1 were used. Samples consisted of disks 16.5 mm in diameter and 2.0 mm in thickness. The results were averaged for each formulation and are shown in Table 3.
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Priority Applications (11)
Application Number | Priority Date | Filing Date | Title |
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US11/494,911 US8247511B2 (en) | 1999-04-12 | 2006-07-28 | Water plasticized high refractive index polymer for ophthalmic applications |
EP07836310A EP2049923A2 (en) | 2006-07-28 | 2007-07-27 | Water plasticized high refractive index polymer for ophthalmic applications |
CNA2007800287423A CN101495887A (zh) | 2006-07-28 | 2007-07-27 | 眼科用水塑化高折射率聚合物 |
BRPI0714948-4A BRPI0714948A2 (pt) | 2006-07-28 | 2007-07-27 | polÍmero de Índice refrativo elevado plastificado por Água para aplicaÇÕes oftÁlmicas |
MX2009000853A MX2009000853A (es) | 2006-07-28 | 2007-07-27 | Polimero de alto indice de refraccion plastificado con agua para aplicaciones oftalmicas. |
RU2009107233/05A RU2009107233A (ru) | 2006-07-28 | 2007-07-27 | Пластифицируемый водой полимер с высоким показателем преломления, для офтальмологического применения |
TR2009/00585T TR200900585T1 (tr) | 2006-07-28 | 2007-07-27 | Oftalmik uygulamalara yönelik suyla plastize edilmiş yüksek refraksiyon endeksli polimer. |
KR1020097004297A KR20090048486A (ko) | 2006-07-28 | 2007-07-27 | 안과 적용을 위한 물에 의해 가소화되는 고굴절률 중합체 |
JP2009522809A JP2009544447A (ja) | 2006-07-28 | 2007-07-27 | 水によって可塑化された眼科用高屈折率ポリマー |
PCT/US2007/016931 WO2008013950A2 (en) | 2006-07-28 | 2007-07-27 | Water plasticized high refractive index polymer for ophthalmic applications |
CA002658229A CA2658229A1 (en) | 2006-07-28 | 2007-07-27 | Water plasticized high refractive index polymer for ophthalmic applications |
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US12875199P | 1999-04-12 | 1999-04-12 | |
US09/358,757 US6281319B1 (en) | 1999-04-12 | 1999-07-22 | Water plasticized high refractive index polymer for ophthalmic applications |
US09/917,971 US7083645B2 (en) | 1999-04-12 | 2001-07-30 | Water plasticized high refractive index polymer for ophthalmic applications |
US11/494,911 US8247511B2 (en) | 1999-04-12 | 2006-07-28 | Water plasticized high refractive index polymer for ophthalmic applications |
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US09/917,971 Continuation-In-Part US7083645B2 (en) | 1999-04-12 | 2001-07-30 | Water plasticized high refractive index polymer for ophthalmic applications |
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US (1) | US8247511B2 (ja) |
EP (1) | EP2049923A2 (ja) |
JP (1) | JP2009544447A (ja) |
KR (1) | KR20090048486A (ja) |
CN (1) | CN101495887A (ja) |
BR (1) | BRPI0714948A2 (ja) |
CA (1) | CA2658229A1 (ja) |
MX (1) | MX2009000853A (ja) |
RU (1) | RU2009107233A (ja) |
TR (1) | TR200900585T1 (ja) |
WO (1) | WO2008013950A2 (ja) |
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US11318226B2 (en) | 2015-11-19 | 2022-05-03 | Eyebright Medical Technology (Beijing) Co., Ltd. | Materials for preparing intraocular lens |
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2006
- 2006-07-28 US US11/494,911 patent/US8247511B2/en not_active Expired - Lifetime
-
2007
- 2007-07-27 CN CNA2007800287423A patent/CN101495887A/zh active Pending
- 2007-07-27 WO PCT/US2007/016931 patent/WO2008013950A2/en active Application Filing
- 2007-07-27 JP JP2009522809A patent/JP2009544447A/ja not_active Withdrawn
- 2007-07-27 RU RU2009107233/05A patent/RU2009107233A/ru not_active Application Discontinuation
- 2007-07-27 KR KR1020097004297A patent/KR20090048486A/ko not_active Application Discontinuation
- 2007-07-27 BR BRPI0714948-4A patent/BRPI0714948A2/pt not_active IP Right Cessation
- 2007-07-27 CA CA002658229A patent/CA2658229A1/en not_active Abandoned
- 2007-07-27 MX MX2009000853A patent/MX2009000853A/es not_active Application Discontinuation
- 2007-07-27 TR TR2009/00585T patent/TR200900585T1/xx unknown
- 2007-07-27 EP EP07836310A patent/EP2049923A2/en not_active Withdrawn
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US11958819B2 (en) | 2015-08-21 | 2024-04-16 | Johnson & Johnson Surgical Vision, Inc. | Compounds for optically active devices |
US11318226B2 (en) | 2015-11-19 | 2022-05-03 | Eyebright Medical Technology (Beijing) Co., Ltd. | Materials for preparing intraocular lens |
US10196470B2 (en) * | 2016-05-16 | 2019-02-05 | Benz Research And Development Corp. | Hydrophobic intraocular lens |
US10899862B2 (en) | 2016-05-16 | 2021-01-26 | Benz Research And Development Corp. | Hydrophobic intraocular lens |
US11702396B2 (en) | 2017-02-15 | 2023-07-18 | Johnson & Johnson Surgical Vision, Inc. | Hydrophobic compounds for optically active devices |
US11753387B2 (en) | 2017-02-15 | 2023-09-12 | Johnson & Johnson Surgical Vision, Inc. | Compounds for optically active devices |
EP3502147A1 (de) | 2017-12-22 | 2019-06-26 | Merck Patent GmbH | Zusammensetzung für ophthalmologische produkte |
WO2019121642A1 (de) | 2017-12-22 | 2019-06-27 | Merck Patent Gmbh | Zusammensetzung für ophthalmologische produkte |
US11359031B2 (en) | 2017-12-22 | 2022-06-14 | Johnson & Johnson Surgical Vision, Inc. | Composition for ophthalmological products |
Also Published As
Publication number | Publication date |
---|---|
KR20090048486A (ko) | 2009-05-13 |
CA2658229A1 (en) | 2008-01-31 |
MX2009000853A (es) | 2009-05-25 |
RU2009107233A (ru) | 2010-09-10 |
WO2008013950A3 (en) | 2008-04-03 |
US20070010883A1 (en) | 2007-01-11 |
WO2008013950A2 (en) | 2008-01-31 |
BRPI0714948A2 (pt) | 2013-06-11 |
TR200900585T1 (tr) | 2009-05-21 |
CN101495887A (zh) | 2009-07-29 |
JP2009544447A (ja) | 2009-12-17 |
EP2049923A2 (en) | 2009-04-22 |
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